Chapter 86 – Parkinson’s Disease

chapter

Parkinson’s Disease

Jing Zhang and Tessandra Stewart

INTRODUCTION

Parkinson’s disease (PD) is one of the most common neuro-logical disorders, affecting around 1% of the population over the age of 65. It is characterized by motor dysfunction result-ing from the progressive loss of nigrostriatal input to the basal ganglia, as well as an array of non-motor symptoms, which likely result from deficits outside the striatum and/or in non- dopaminergic systems (Lang and Obeso, 2004). Familial

transmission occurs in a minority of cases, and several gene mutations causing inherited PD have been identified (Bekris et al., 2010). These include mutations in SNCA, which codes for α-synuclein (a small protein found in Lewy bodies, which characterize brain pathology of PD); leucine-rich repeat kinase (LRRK2), which encodes an apparent tyrosine-kinase like pro-tein; PARK2, encoding the E3 ubiquitin ligase parkin; PINK1, which encodes a mitochondria-localized kinase believed to function upstream of parkin; and DJ-1, which codes for a cyto-solic protein that can translocate to mitochondria and appears to have antioxidant activity. However, like many other com-plex neurological disorders of adult life (see Chapter 84), most PD cases are idiopathic and are believed to result from com-plex interactions of genetic and environmental risk factors (Horowitz and Greenamyre, 2010; Vance et al., 2010). Although precise mechanisms responsible for PD development remain undefined, the common underlying pathways in sporadic and

genetic PD are believed to relate to mitochondrial dysfunction, oxidative stress, and mishandling of protein degradation by an impaired ubiquitin-proteosome system (UPS).

THE NEED FOR RELIABLE PARKINSON’S DISEASE BIOMARKERS

The development of reliable biomarkers for PD is vital for understanding its pathogenesis and for improving diagnos-tic and predictive criteria. Currently, diagnosis of PD relies on assessment of clinical symptoms, which can overlap signifi-cantly with other disorders, including multiple system atrophy (MSA) and progressive supra-nuclear palsy (PSP). Additionally, identification of markers to monitor disease outcome would facilitate personalization of treatment. Of particular interest are measures allowing prediction of disease progression, as this would aid physicians in assessing prognosis and manag-ing the disease. However, there are currently no established biomarkers capable of diagnosing PD patients, predicting or categorizing PD progression, or identifying non-symptomatic patients at risk of developing sporadic PD. Therefore, the development of objective criteria for these goals is a major area of study.

The advent of “omic” technologies provides an ideal opportunity for the development of biomarkers. These

Copyright © 2013

, Elsevier Inc.

All rights reserved.

Genomic and Personalized Medicine, 2nd edition

by Ginsburg & Willard. DOI: doc.guandang.net